Although integrins are known to mediate invasion and metastasis, recent studies reveal new ways in which they contribute to squamous-cell carcinoma. Integrin mutation or upregulation can expand the tumour stem-cell compartment by inhibiting differentiation or apoptosis. Integrins that are expressed by differentiated cells can stimulate or inhibit the proliferation of neighbouring tumour stem cells. These findings provide a mechanistic basis for the well-established links between altered integrin expression and tumour prognosis.